Corneal confocal microscopy may help to distinguish Multiple System Atrophy from Parkinson's disease.

Multiple system atrophy (MSA) and Parkinson's disease (PD) have clinical overlapping symptoms, which makes differential diagnosis difficult. Our research aimed to distinguish MSA from PD using corneal confocal microscopy (CCM), a noninvasive and objective test. The study included 63 PD patients, 30 MSA patients, and 31 healthy controls (HC). When recruiting PD and MSA, questionnaires were conducted on motor and non-motor functions, such as autonomic and cognitive functions. Participants underwent CCM to quantify the corneal nerve fibers. Corneal nerve fiber density (CNFD) and corneal nerve fiber length (CNFL) values in MSA are lower than PD (MSA vs. PD: CNFD, 20.68 ± 6.70 vs. 24.64 ± 6.43 no./mm2, p < 0.05; CNFL, 12.01 ± 3.25 vs. 14.17 ± 3.52 no./mm2, p < 0.05). In MSA + PD (combined), there is a negative correlation between CNFD and the Orthostatic Grading Scale (OGS) (r = -0.284, p = 0.007). Similarly, CNFD in the only MSA group was negatively correlated with the Unified Multiple System Atrophy Rating Scale I and II (r = -0.391, p = 0.044; r = -0.382, p = 0.049). CNFD and CNFL were inversely associated with MSA (CNFD: ß = -0.071; OR, 0.932; 95% CI, 0.872 ~ 0.996; p = 0.038; CNFL: ß = -0.135; OR, 0.874; 95% CI, 0.768-0.994; p = 0.040). Furthermore, we found the area under the receiver operating characteristic curve (ROC) of CNFL was the largest, 72.01%. The CCM could be an objective and sensitive biomarker to distinguish MSA from PD. It visually reflects a more severe degeneration in MSA compared to PD.

High-frequency rTMS over bilateral primary motor cortex improves freezing of gait and emotion regulation in patients with Parkinson's disease: a randomized controlled trial.

Background: Freezing of gait (FOG) is a common and disabling phenomenon in patients with Parkinson's disease (PD), but effective treatment approach remains inconclusive. Dysfunctional emotional factors play a key role in FOG. Since primary motor cortex (M1) connects with prefrontal areas via the frontal longitudinal system, where are responsible for emotional regulation, we hypothesized M1 may be a potential neuromodulation target for FOG therapy. The purpose of this study is to explore whether high-frequency rTMS over bilateral M1 could relieve FOG and emotional dysregulation in patients with PD. Methods: This study is a single-center, randomized double-blind clinical trial. Forty-eight patients with PD and FOG from the Affiliated Hospital of Xuzhou Medical University were randomly assigned to receive 10 sessions of either active (N = 24) or sham (N = 24) 10 Hz rTMS over the bilateral M1. Patients were evaluated at baseline (T0), after the last session of treatment (T1) and 30 days after the last session (T2). The primary outcomes were Freezing of Gait Questionnaire (FOGQ) scores, with Timed Up and Go Test (TUG) time, Standing-Start 180° Turn (SS-180) time, SS-180 steps, United Parkinson Disease Rating Scales (UPDRS) III, Hamilton Depression scale (HAMD)-24 and Hamilton Anxiety scale (HAMA)-14 as secondary outcomes. Results: Two patients in each group dropped out at T2 and no serious adverse events were reported by any subject. Two-way repeated ANOVAs revealed significant group × time interactions in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14. Post-hoc analyses showed that compared to T0, the active group exhibited remarkable improvements in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14 at T1 and T2. No significant improvement was found in the sham group. The Spearman correlation analysis revealed a significantly positive association between the changes in HAMD-24 and HAMA-14 scores and FOGQ scores at T1. Conclusion: High-frequency rTMS over bilateral M1 can improve FOG and reduce depression and anxiety in patients with PD.

Relationship between increased serum neurofilament light chain and glial fibrillary acidic protein levels with non-motor symptoms in patients with Parkinson's disease.

BACKGROUND: This study set out to investigate the relationship between serum neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and various non-motor symptoms (NMSs) in patients with Parkinson's disease (PD). METHODS: The study included 37 healthy controls (HCs) and 51 PD patients. Clinical assessments of PD symptoms were conducted for all PD patients. The NMSS was utilised to evaluate the NMS burden (NMSB) in individuals. Based on the severity of NMSB, we further categorised the PD group into two subgroups: mild-moderate NMSB group and severe-very severe NMSB group. The amounts of NFL and GFAP in the serum were measured using an extremely sensitive single molecule array (Simoa) method. Statistical analyses were performed on the collected data using SPSS 26.0 and R (version 3.6.3). RESULTS: Serum GFAP and NFL levels in the PD group with severe-very severe NMSB were significantly higher than those in the mild-moderate NMSB group (GFAP: P < 0.007; NFL: P < 0.009). Serum NFL and GFAP levels had positive correlations with NMSS total scores (GFAP: r = 0.326, P = 0.020; NFL: r = 0.318, P = 0.023) and multiple subdomains. The relationship between the attention/memory domains of NMSS and NFL levels is significantly positive (r = 0.283, P = 0.044). Similarly, the mood/apathy domains of NMSS are also significantly positively correlated with GFAP levels (r = 0.441, P = 0.001). Patients with emotional problems or cognitive impairment had higher GFAP or NFL levels, respectively. Furthermore, it has been demonstrated that NMSs play a mediating role in the quality of life of patients with PD. Moreover, the combination of NFL and GFAP has proven to be more effective than using a single component in identifying PD patients with severe-very severe NMSB. CONCLUSIONS: The severity of NMSs in PD patients, particularly cognitive and emotional symptoms, was found to be associated with the levels of serum NFL and GFAP. This study marks the first attempt to examine the connection between NMSs of PD and the simultaneous identification of NFL and GFAP levels.

An interactive web application to identify early Parkinsonian non-tremor-dominant subtypes.

BACKGROUND: Parkinson's disease (PD) patients with tremor-dominant (TD) and non-tremor-dominant (NTD) subtypes exhibit heterogeneity. Rapid identification of different motor subtypes may help to develop personalized treatment plans. METHODS: The data were acquired from the Parkinson's Disease Progression Marker Initiative (PPMI). Following the identification of predictors utilizing recursive feature elimination (RFE), seven classical machine learning (ML) models, including logistic regression, support vector machine, decision tree, random forest, extreme gradient boosting, etc., were trained to predict patients' motor subtypes, evaluating the performance of models through the area under the receiver operating characteristic curve (AUC) and validating by the follow-up data. RESULTS: The feature subset engendered by RFE encompassed 20 features, comprising some clinical assessments and cerebrospinal fluid α-synuclein (CSF α-syn). ML models fitted in the RFE subset performed better in the test and validation sets. The best performing model was support vector machines with the polynomial kernel (P-SVM), achieving an AUC of 0.898. Five-fold repeated cross-validation showed the P-SVM model with CSF α-syn performed better than the model without CSF α-syn (P = 0.034). The Shapley additive explanation plot (SHAP) illustrated that how the levels of each feature affect the predicted probability as NTD subtypes. CONCLUSION: An interactive web application was developed based on the P-SVM model constructed from feature subset by RFE. It can identify the current motor subtypes of PD patients, making it easier to understand the status of patients and develop personalized treatment plans.

Utility of serum neurofilament light chain and glial fibrillary acidic protein as diagnostic biomarkers of freezing of gait in Parkinson's disease.

Freezing of gait (FOG) is one of the most distressing features of Parkinson's disease (PD), increasing the risks of fractures and seriously affecting patients' quality of life. We aimed to examine the potential diagnostic roles of serum neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) in PD patients with FOG (PD-FOG). We included 99 patients, comprising 54 PD patients without FOG (PD-NoFOG), 45 PD-FOG and 37 healthy controls (HCs). Our results indicated serum markers were significantly higher in PD-FOG and postural instability and gait difficulty (PIGD) motor subtype patients than in PD-NoFOG and non-PIGD subtype patients (P < 0.05), respectively. Patients with high concentrations of the markers NFL and GFAP had higher PIGD scores and greater FOG severity than those with low concentrations. Moreover, serum levels of both NFL and GFAP were significantly positively associated with age, FOG severity, PD-FOG status, and negatively associated with Mini-Mental State Examination (MMSE) scores. Logistic regression analysis identified serum levels of NFL and GFAP as independent risk factors for PD-FOG. Mediation analysis revealed that MMSE scores fully mediated the relationship between serum GFAP levels and FOG-Q scores, accounting for 33.33% of the total effects (indirect effect = 0.01, 95% CI 0.01-0.02). NFL levels differentiated PD-FOG from PD-NoFOG with reliable diagnostic accuracy (AUC 0.75, 95% CI 0.66-0.84), and the combination of NFL, GFAP, duration and MMSE scores demonstrated high accuracy (AUC 0.84, 95% CI 0.76-0.91). Our findings support the notion that NFL and GFAP may be potential biomarkers for the diagnosis of PD-FOG.

Association between serum neurofilament light chain levels and sleep disorders in patients with Parkinson's disease.

OBJECTIVES: This study aimed to investigate the levels of serum neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) in patients with Parkinson's disease (PD) and PD patients with sleep disorders (PD-SD), as well as the relationship between these proteins and sleep disorders in PD patients. METHODS: A total of 96 PD patients and 38 healthy controls (HC) were included in this study, of which 70 PD patients experienced sleep disorders. Both motor symptoms and sleep conditions were assessed in all PD patients. The ultrasensitive single molecule array (SIMOA) technique was used to quantify NFL and GFAP in the serum. All data were statistically analyzed using SPSS 23.0. RESULTS: Serum NFL and GFAP levels were significantly higher in PD patients than in HC. Similarly, PD-SD patients exhibited higher levels of these two proteins than PD patients without sleep disorders (PD-NSD). In addition, both serum GFAP and NFL were significantly associated with sleep-related scales in PD patients. After covariate-adjusted binary logistic regression analysis, NFL remained statistically significant in PD patients with or without sleep disorders, unlike GFAP. CONCLUSIONS: Our findings substantiate that serum NFL and GFAP levels are elevated in PD and PD-SD, suggesting neurological axon damage in PD patients, which may be more severe in PD-SD than in PD-NSD. These findings may affect disease diagnosis and provide the foothold for future studies on the underlying mechanisms.

The relationship between serum neurofilament light chain and glial fibrillary acidic protein with the REM sleep behavior disorder subtype of Parkinson's disease.

Studies have shown that rapid eye movement (REM) sleep behavior disorder (RBD) is a subtype of Parkinson's disease (PD) characterized by severe cognitive impairment and rapid disease progression. However, reliable biological markers are lacking presently. Neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) have been widely studied as biomarkers of cognition impairment. This study aimed to find biomarkers for the RBD subtype of PD by investigating the possible relationship between serum NFL, GFAP levels, and the RBD subtype. A total of 109 PD patients and 37 healthy controls (HCs) were included, and their clinical characteristics were evaluated. PD patients were divided into two groups based on whether they had probable RBD or not. Serum NFL and GFAP levels were measured using the ultrasensitive single molecule array (Simoa) platform. The obtained data were statistically analyzed using SPSS 25.0 (IBM, Chicago, IL, USA). NFL and GFAP in the PD-RBD group were elevated compared with the PD-nRBD and control groups. Moreover, serum NFL and GFAP levels positively correlated with RBD. The combination of NFL and GFAP showed good performance in identifying PD-RBD patients from PD-nRBD. After considering potential confounding factors such as age, and disease duration, serum NFL and GFAP emerged as independent risk factors for RBD. Serum NFL and GFAP were related to RBD in PD patients. Concludingly, serum NFL and GFAP might serve as promising biomarkers for the RBD subtype of PD.

Association of serum neurofilament light chain and glial fibrillary acidic protein levels with cognitive decline in Parkinson's disease.

OBJECTIVES: To investigate whether serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) levels are associated with motor and cognitive function in Parkinson's disease (PD). METHODS: This cross-sectional study recruited 140 participants, including 103 PD patients and 37 healthy controls (HC). Serum NfL and GFAP levels were measured using the ultrasensitive single-molecule array (Simoa) technique. Motor and cognitive function were evaluated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III) and Beijing version of the Montreal Cognitive Assessment (MoCA). Spearman's correlation analyses were used to determine the correlation between serum NfL and GFAP levels and clinical features in PD patients. Binary logistic regression analysis was used to assess the association between serum biomarkers and cognitive impairment in PD patients. RESULTS: We observed significantly higher serum NfL and GFAP levels in PD patients than in HC (p < 0.001). Serum NfL and GFAP levels were negatively correlated with MoCA scores (NfL: r =  - 0.472, p < 0.001; r = 0.395, p < 0.001) and multiple cognitive domains and showed no correlation with motor symptom severity after adjusting for age and sex. Binary logistic regression analysis showed that the serum NfL and GFAP levels were independent contributors to PD with dementia (p < 0.05). CONCLUSIONS: Both serum NfL and GFAP levels correlated with cognitive impairment, but not motor symptoms, in PD patients. Serum NfL and GFAP levels can serve as biomarkers for PD patients at risk of cognitive decline.

Activating PV-positive neurons in ventral thalamic reticular nucleus reduces pain sensitivity in mice.

Previous studies have demonstrated that thalamic reticular nucleus (TRN) and the sub-nuclei play important roles in pain sensation. Our previous findings showed that activating parvalbumin-positive (PV+) neurons in dorsal sector of TRN (dTRN) could reduce the pain threshold and consequently increase the pain sensitivity of mice. Recent studies have shown that activation of GABAergic projection of TRN to ventrobasal thalamus (VB) alleviated pathological pain. GABAergic neurons in TRN are mainly PV+ neurons. However, the exact roles of ventral TRN (vTRN) PV+ neurons in pain sensation remain unclear. In this study, the designer receptors exclusively activated by designer drugs (DREADD) method was used to activate the PV+ neurons in vTRN of PV-Cre transgenic mice, and the mechanical threshold and thermal latency were measured to investigate the regulatory effects of vTRN on pain sensitivity in mice. Thereafter, PV-Cre transgenic mice, conditional anterograde axonal tract tracing, and immunohistochemistry were used to investigate the distribution of PV+ neurons fibers in vTRN. The results showed that the activation of PV+ neurons in vTRN increased the mechanical threshold and thermal latency, which indicated reduction of pain sensitivity. The fibers of these neurons mainly projected to ventral posterolateral thalamic nucleus (VPL), ventral posteromedial thalamic nucleus (VPM), ventrolateral thalamic nucleus (VL), centrolateral thalamic nucleus (CL) and various other brain regions. These findings indicated that activation of PV+ neurons in the vTRN decreased pain sensitivity in mice, which provided additional evidence on the mechanisms of PV+ neurons of TRN in regulating neuralgia.

Cathepsin L-containing exosomes from α-synuclein-activated microglia induce neurotoxicity through the P2X7 receptor.

Uncontrolled microglial activation is pivotal to the pathogenesis of Parkinson's disease (PD), which can secrete Cathepsin L (CTSL) to affect the survival of neurons in the PD patients; however, the precise mechanism has yet to be determined. We demonstrated for the first time that CTSL was mostly released by exosomes derived from α-Syn-activated microglia, resulting in neuronal damage and death. The elevation of CTSL activity was blocked by GW4869, suggesting a critical role for exosomes in mediating CTSL release. Furthermore, the P2X7R/PI3K/AKT signalling pathway was identified as the underlying molecular mechanism since specific antagonists of this signalling pathway, P2X7R knockdown and exosome release inhibitors significantly reduced the injury to cultured mouse cortical neurons. Our study suggests that increased extracellular release of CTSL from α-Syn-activated microglia through exosomes amplifies and aggravates of the neurotoxic effect of microglia, implying that CTSL may be involved in a fresh mechanism of PD pathogenesis, and serve as a potential biomarker and a target for PD drug development.

Correlation between serum 25(OH)D and cognitive impairment in Parkinson's disease.

This study aimed to investigate the relationship between serum 25(OH)D and cognitive impairment in patients with Parkinson's disease (PD), hoping to provide possible ideas for the diagnosis and prevention of PD with cognitive impairment. Vitamin D is a neurosteroid with neurotrophic and neuroprotective functions, playing an important role in PD and its progression. In the present study, serum 25(OH)D levels were significantly decreased in PD patients (45.86 ± 14.81 nmol/L)compared to healthy controls(56.54 ± 14.00 nmol/L) (P < 0.001), and significant differences were also observed in PD patients with normal cognition (PD-NC), PD patients with mild cognitive impairment (PD-MCI)and PD patients with dementia (PDD)(P < 0.05). Moreover, there was a positive correlation between serum 25(OH)D levels and Montreal cognitive assessment(MoCA) scores (r = 0.489,P < 0.001).The increased serum 25(OH)D was an independent protective factor of cognitive impairment in PD (OR = 0. 949, P = 0.005), and the sensitivity, specificity, and AUC under the ROC curve area of serum 25(OH)D were 53.3%, 86.5%, and 0.713, respectively. These findings support the relationship between cognitive impairment and Vitamin D in PD patients. Serum 25(OH)D may be a useful biomarker for diagnosing cognitive impairment in patients with PD.

Comparative Analysis of Acute Levodopa Challenge Test and the Outcomes of Deep Brain Stimulation in Parkinson's Disease.

BACKGROUND: We study the correlation between the preoperative levodopa challenge test and the efficacy of deep brain stimulation (DBS) surgery in Parkinson's disease (PD). METHODS: Fifty patients with PD who underwent DBS treatment in our hospital from October 2016 to October 2017 were enrolled in this study. Using the Unified Parkinson Disease Rating Scale-III (UPDRS-III) as an indicator, we analyzed the improvement in motor symptoms on the levodopa challenge test and by DBS surgery. We also discussed the correlation between the effects of the levodopa challenge test and DBS surgery. RESULTS: There was no correlation between the results of the levodopa challenge test and DBS surgery. There was a linear correlation between muscle rigidity and bradykinesia, whereas the linear correlation between other symptoms was weak. CONCLUSION: The levodopa challenge test can be used as a screening tool for patients undergoing DBS surgery, and can predict the degree of improvement in muscle rigidity and bradykinesia surgery. However, the prediction of the degree of improvement of total motor symptoms is poor.

Functional MRI in Parkinson's disease with freezing of gait: a systematic review of the literature.

BACKGROUND: Freezing of gait (FOG), a common and disabling symptom of Parkinson's disease (PD), is characterized by an episodic inability to generate effective stepping. Functional MRI (fMRI) has been used to evaluate abnormal brain connectivity patterns at rest and brain activation patterns during specific tasks in patients with PD-FOG. This review has examined the existing functional neuroimaging literature in PD-FOG, including those with treatment. Summarizing these articles provides an opportunity for a better understanding of the underlying pathophysiology in PD-FOG. METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we performed a literature review of studies using fMRI to investigate the underlying pathophysiological mechanisms of PD-FOG. RESULTS: We initially identified 201 documents. After excluding the duplicates, reviews, and other irrelevant articles, 39 articles were finally identified, including 18 task-based fMRI studies and 21 resting-state fMRI studies. CONCLUSIONS: Studies using fMRI techniques to evaluate PD-FOG have found dysfunctional connectivity in widespread cortical and subcortical regions. Standardized imaging protocols and detailed subtypes of PD-FOG are furthered required to elucidate current findings.

Differential efferent projections of GABAergic neurons in the basolateral and central nucleus of amygdala in mice.

The Basolateral amygdala (BLA) and central nucleus of the amygdala (CEA) have been proved to play a key role in the control of anxiety, stress and fear-related behaviors. BLA is a cortex-like complex consisting of both γ-aminobutyric acidergic (GABAergic) interneurons and glutamatergic neurons. The CEA is a striatum-like output of the amygdala, consisting almost exclusively of GABAergic medium spiny neurons. In this study, we explored the morphology and axonal projections of the GABAergic neurons in BLA and CEA, using conditional anterograde axonal tracing, immunohistochemistry, and VGAT-Cre transgenic mice to further understand their functional roles. We found that the axonal projections of GABAergic neurons from the BLA mainly distributed to the forebrain, whilst GABAergic neurons from the CEA distributed to the forebrain, midbrain and brainstem. In the forebrain, the axonal projections of GABAergic neurons from the BLA projected to the anterior olfactory nucleus, the cerebral cortex, the septum, the striatum, the thalamus, the amygdala and the hippocampus. The axonal projections of GABAergic neurons from the CEA distributed to the nuclei of the prefrontal cortex, the bed nucleus of the stria terminalis, the hypothalamus and the thalamus. In the midbrain and brainstem, the axonal projections of GABAergic neurons from the CEA were found in the periaqueductal gray, the substantia nigra, and the locus coeruleus. These data reveal the neuroanatomical basis for exploring the function of GABAergic neurons in the BLA and CEA, particularly during the processing of fear-related behavior.

A novel anti-HER2 antibody GB235 reverses Trastuzumab resistance in HER2-expressing tumor cells in vitro and in vivo.

HER2 overexpression is frequently associated with tumor metastasis and poor prognosis of breast cancer. More evidence indicates that HER3 is involved in HER2-resistant therapies. Combination treatments with two or more different monoclonal antibodies are a promising strategy to overcome resistance to HER2 therapies. We presented a novel fully human HER2-targeted monoclonal antibody, GB235, screened from a phage-display library against the HER2 antigen. GB235 in combination with Trastuzumab overcomes resistance in HER2-positive tumors and results in more sustained inhibition of tumor growth over time. The competition binding assay showed that the epitopes of GB235 do not overlap with those of Pertuzumab and Trastuzumab on HER2. Further HER2 mutagenesis results revealed that the binding epitopes of GB235 were located in the domain III of HER2. The mechanism of action of GB235 in blocking HER2-driven tumors is different from the mechanisms of Trastuzumab or Pertuzumab. GB235 does not affect the heterodimerization of HER2 and HER3, whereas the GB235 combined treatment with Trastuzumab significantly inhibited heregulin-induced HER3 phosphorylation and downstream signaling. Moreover, GB235 in combination with Trastuzumab reversed the resistance to heregulin-induced proliferation in HER2-overexpressing cancer cell lines. GB235 combined with Trastuzumab treatment in xenograft models resulted in improved antitumor activity. Complete tumor suppression was observed in the HER2-positive NCI-N87 xenograft model treated with the combination treatment with GB235 and Trastuzumab. In a Trastuzumab-resistant patient-derived tumor xenograft model GA0060, GB235 plus Trastuzumab reversed the resistance to Trastuzumab monotherapy. Because GB235 showed a different working mechanism with Pertuzumab and Trastuzumab, these agents can be considered complementary therapy against HER2 overexpression tumors.

An analysis of the clinical and imaging features of mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS).

Objective: To investigate the clinical features and imaging characteristics of mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS).Methods: Seventeen patients with MELAS diagnosed in the Affiliated Hospital of Xuzhou Medical University from July 2014 to August 2018 were enrolled in this study and their clinical manifestations, imaging and histopathological features were retrospectively analysed. We also discussed and summarised the related literature.Results: All of the 12 patients had seizures; stroke-like episodes in 12 cases; audio-visual impairment in 12 cases; headache in six cases; dysplasia in four cases; mental retardation in three cases; ataxia in two cases. On cranial magnetic resonance (MR) scans, the most common manifestations were in temporal-occipital-parietal lobe, cortical or subcortical areas as well as frontal lobe, thalamus, and basal ganglia showing long or equal T1 signals, long T2 signals, and hyperintense or iso-intense diffusion-weighted imaging (DWI) signals accompanied by ventricular enlargement and brain atrophy. MR spectroscopy showed that lactic acid peaks could be found in lesion sites, normal brain tissues, and cerebrospinal fluid. Muscle biopsy and genetic testing are the gold standard for diagnosing MELAS, muscle biopsy revealed COX-negative muscle fibres and SDH-stained red ragged fibres (RRF) under the sarcolemma. Mutations of mtDNA A3243G locus were common on gene testing. Improvement of mitochondrial function was observed after symptomatic and supportive treatment.Conclusion: MELAS should be considered for patients with epileptic seizures, headache, stroke-like episodes, extraocular palsy, cognitive decline and other clinical manifestations with the lesion located in the temporal-occipital-parietal lobe regardless of the distribution of blood vessels, and further examinations including muscle biopsy and gene testing should be performed to confirm the diagnosis.

An Analysis of Clinical Characteristics of Rare Bilateral Cerebral Peduncular Infarction.

Objective: To investigate the anatomical characteristics, clinical manifestations, and imaging features of bilateral cerebral peduncular infarction. Methods: A retrospective analysis was performed on 11 patients diagnosed with bilateral cerebral peduncular infarction in the Affiliated Hospital of Xuzhou Medical University from December 2014 to December 2018. Their clinical and imaging features were analyzed and summarized in combination with the relevant national and international literature. Results: Among all the patients, there were eight cases with a history of hypertension, four cases with a history of diabetes mellitus, and four cases with a history of smoking. Conscious disturbance was observed in nine cases, quadriplegia in seven cases, pseudobulbar paralysis in three cases, and ataxia in one case. Brain magnetic resonance (MR) scans of bilateral cerebral peduncles showed patchy abnormal shadows with a hypointense signal on T1-weighted imaging (T1WI) and apparent diffusion coefficient (ADC) and hyperintense signal on T2-weighted imaging (T2WI), fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI). Computed tomography angiography (CTA) scans of head and neck showed severe stenosis or occlusion of vertebral artery, basilar artery, or posterior cerebral artery. All the patients received standardized treatment for cerebral infarction. Six patients died while five were left disabled. Conclusion: Bilateral cerebral peduncle infarction may be related to cerebral perfusion insufficiency caused by the stenosis or occlusion of vertebrobasilar artery and its branches. The main clinical manifestations are locked-in syndrome and persistent vegetative state. The specific imaging feature of "Mickey Mouse ear"-like infarction is associated with a poor prognosis.

An Efficient Somatic Embryo Liquid Culture System for Potential Use in Large-Scale and Synchronic Production of Anthurium andraeanum Seedlings.

Anthurium andraeanum Lind. is the second most important tropical flower in the world flower market. Somatic embryogenesis and plant regeneration in Anthurium has been reported previously; however, a stable and effective method for its commercial use has not been available. In this study, an efficient somatic embryogenesis and liquid culture system for large-scale production of A. andraeanum seedlings was achieved. Building on previous research, this study investigated the main factors for proembryogenic mass (PEM) proliferation, somatic embryo (SE) development, and SE germination in Anthurium. The results showed that relatively low concentrations of plant growth regulators, mineral nutrition, and sucrose promoted PEM proliferation, SE formation, and germination in a liquid culture system. This system can be described as follows: PEMs were induced from leaf blade explants on Murashige & Skoog (MS) medium with half-strength MS macronutrients (1/2 MS) containing 2.0 mg L-1 2,4-dichlorophenoxyacetic acid (2,4-D), 0.5 mg L-1 kinetin (KT), and 3% sucrose and were proliferated in ½ MS liquid medium containing 1.0 mg L-1 2,4-D, 0.5 mg L-1 KT, and 3% sucrose. The highest proliferation coefficients were 5.11-5.16. PEMs were then transferred to MS medium with 1/8 MS macronutrients (1/8 MS) liquid medium containing 1% sucrose to develop into globular embryos and mature embryos. Finally, the mature embryos were placed on four layers of absorbent filter paper saturated with 1/8 MS liquid medium containing 1% sucrose for germination, and an average of 60 seedlings per gram SEs was obtained. This liquid culture system can be used in large-scale and synchronic production of Anthurium seedlings.

DJ-1 Inhibits α-Synuclein Aggregation by Regulating Chaperone-Mediated Autophagy.

α-Synuclein misfolding and aggregation play an important role in the pathogenesis of Parkinson's disease (PD). Loss of function and mutation of the PARK7/DJ-1 gene cause early-onset familial PD. DJ-1 can inhibit α-synuclein aggregation, and may function at an early step in the aggregation process. Soluble wild-type (WT) α-synuclein is mainly degraded by chaperone-mediated autophagy (CMA), and impairment of CMA is closely related to the pathogenesis of PD. Here, we investigated whether DJ-1 could reduce α-synuclein accumulation and aggregation by CMA. DJ-1 knockout mice and DJ-1 siRNA knockdown SH-SY5Y cells were used to investigate the potential mechanisms underlying the relationship between DJ-1 deficiency and α-synuclein aggregation. First, we confirmed that DJ-1 deficiency increased the accumulation and aggregation of α-synuclein in both SH-SY5Y cells and PD animal models, and overexpression of DJ-1 in vitro effectively decreased α-synuclein levels. α-Synuclein overexpression activated CMA by elevating the levels of lysosome-associated membrane protein type-2A (LAMP2A), but DJ-1 deficiency suppressed upregulation of LAMP2A. DJ-1 deficiency downregulated the level of lysosomal 70 kDa heat-shock cognate protein (HSC70) but not the levels of that in homogenates. Further studies showed that DJ-1 deficiency accelerated the degradation of LAMP2A in lysosomes, leading to the aggregation of α-synuclein. Our study suggests that DJ-1 deficiency aggravates α-synuclein aggregation by inhibiting the activation of CMA and provides further evidence of the molecular interaction between PD-related proteins via the CMA pathway.

Meta-analysis on the prevalence of REM sleep behavior disorder symptoms in Parkinson's disease.

BACKGROUND: Our study was aimed to evaluate the risk of a selected non-motor symptom, namely rapid eye movement behavior disorder (RBD) symptoms, among patients with newly diagnosed Parkinson disease compared with health controls. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for meta-analysis and Cochrane manual were followed. Studies on RBD symptoms and PD were searched using PubMed, Embase, Web of Science and Cochrane library databases. All studies were published before August 3rd, 2016. Eligible studies were those that reported a prevalence of RBD symptoms among newly diagnosed PD and health control. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by random-effected models. Heterogeneity across studies was assessed using Cochran Q and I2 statistics. RESULTS: We identified eight studies including 2462 PD patients and 3818 health controls. The overall prevalence of RBD symptoms in PD was 582/2462 (23.6%) compared to 131/3818 (3.4%) in control. And the pooled OR was 5.69 (95% CI 3.60 to 9.00; p = 0.001) with a moderate heterogeneity I2 = 70.5%. After excluding the study of low weight, the overall polled OR was 3.54 (95% CI 2.77 to 4.52; p < 0.00001) and the heterogeneity was completely eliminated (I2 = 0%). CONCLUSIONS: RBD symptoms are common non-motor symptoms of PD, and people with PD are at a higher risk of developing RBD. Further studies are needed to understand the natural history of RBD symptoms in PD and its etiological and clinical implications.